Inflammatory bowel disease (IBD) is an incurable idiopathic disease in which chronic inflammation or ulceration at the mucous membrane of the large and small intestines is caused, and diarrhea or bloody stool continues over a long period with recurrence repeated. This disease is designated as one of the specified diseases in Japan, and a medical care certificate is issued to each patient under the research project for the disease. IBD includes two major types of diseases, that is, Crohn's disease (CD) and ulcerative colitis (UC).
Crohn's disease, which is also called regional enteritis, granulomatous ileitis or ileocolitis, is a chronic inflammation developed on the intestinal wall, or even on any site of the digestive tract. Ulcerative colitis is a chronic disease wherein inflammation occurs in the large intestine to produce an ulcer, resulting in bloody diarrhea, severe abdominal pain, or an attack accompanied with fever. The numbers of the patients of the two diseases are on increase in Japan though they are not higher than those in Europe or the United States. In particular, the numbers of the patients were about 73,000 (in the year 2001) for ulcerative colitis, and about 21,000 (in the year 2001) for Crohn's disease. Furthermore, the number of the medical care certificates issued for ulcerative colitis was ranked on the first place, and the number issued for Crohn's disease was ranked on the eighth place among the 46 specified diseases.
Since the cause of inflammatory bowel disease is unknown as described above, conventional therapeutic agents for diarrhea and the like are not effective. For the treatment of inflammatory bowel disease, aminosalicylic acid preparations (sulfasalazine, 5-aminosalicylic acid) and corticosteroid preparations have been widely used from the past as first-line and second-line drugs. In addition, in a severe case, immunosuppressants (azathioprine, 6-mercaptopurine, and the like), and anti-cytokine preparations have been used. Sulfasalazine and 5-aminosalicylic acid are widely used as an aminosalicylic acid preparation, however, in about 50% of the patients administered with them, they cause digestive organ disorders such as nausea, vomiting, anorexia and hepatic function disorders, and blood system disorders such as agranulocytosis, hemolytic anemia, and folic acid deficiency anemia. Furthermore, since they have salicylic acid skeleton, they are likely to manifest adverse effects in a case that shows hypersensitive reaction to salicylic acid-based drugs, and may cause diarrhea, abdominal pain, amylase increase, renal disorders and the like. Sulfasalazine may cause adverse effects such as male infertility and colored urine, which may become great mental stresses as well to the patients. Corticosteroid preparations have various adverse effects such as osteoporosis, growth impairment, secondary adrenal insufficiency, glucose intolerance, and hypertension. Furthermore, they also have a problem that they have no effects of maintaining the remission of CD or UC. On the other hand, the anti-cytokine therapy is new and totally different from such conventional ones, and the drug that first came out is infliximab which is a chimeric anti-human TNF-α monoclonal antibody. It has been reported that it is effective for the patients with Crohn's disease who have steroid resistance rated as moderate to severe (Non-patent Document 1), and that it is also effective for maintaining the remission (Non-patent Document 2). Adverse effects of it such as hypertension, nausea, rash, fever, headache, and eczema are known. Furthermore, since infliximab is a chimeric antibody, it may show antigenicity, and sometimes cause acute ultra-hypersensitive reaction. Furthermore, recently, infection such that it needs antibiotics or carcinogenicity becomes issues.    [Non-patent Document 1] N. Engl. J. Med., Vol. 337, page 1029,    [Non-patent Document 2] Gastroenterology, Vol. 117, page 761, 1999